BAX Target Analysis Report Summary
About the Target
Based on the provided context information, several key viewpoints regarding BAX can be summarized as follows:
BAX is involved in apoptotic pathways induced by pro-apoptotic proteins, particularly through mitochondrial damage [1].
BH3-only proteins, such as BIM, BID, BAD, PUMA, and NOXA, play a role in regulating BAX-mediated apoptosis. Displacement of BH3-only proteins from anti-apoptotic counterparts can induce apoptosis, and their release can be facilitated by BH3 mimetics [2].
MDM34 and other ERMES components are necessary for BAX's mitochondrial relocation, with disruptions in these components affecting the rate of transfer to the outer mitochondrial membrane (OMM) [3].
Activation of ROS, down-regulation of Bcl-2/BAX ratio, and disruption of mitochondrial integrity can lead to the release of pro-apoptotic proteins, ultimately activating caspases and inducing apoptosis [4].
In some types of carcinomas, there is an imbalance between BCL2 and BAX expression, leading to insensitivity to apoptosis [5].
These viewpoints provide an overview of the role of BAX in apoptotic pathways, its regulation by BH3-only proteins and BH3 mimetics, its mitochondrial relocation, and its involvement in apoptosis in both healthy cells and cancer cells.
Based on the provided context information, the key viewpoints regarding BAX are as follows:
Bax phosphorylation by Akt switches its activity from pro- to anti-apoptotic. In cells with upregulated Akt signaling, Bax is phosphorylated at position S184 by Akt, which prevents Bax from inserting into the mitochondrial outer membrane. This phosphorylation also sequesters BH3 proteins that would normally activate non-phosphorylated Bax and Bak, making cells resistant to pro-apoptotic signaling [6].
In MCF-7 cells, MLL treatment leads to the upregulation of MMP-9, which causes extracellular matrix (ECM) degradation and reduced FN expression. This reduction in FN levels inhibits the interaction with the integrin receptor and downstream signaling, leading to decreased expression of PI3K and Akt phosphorylation. In the unphosphorylated state, Akt promotes the expression of proapoptotic Bax and caspase 9, inducing programmed cell death or anoikis [7].
Bcl-xL and Bcl-xS are isoforms involved in the intrinsic apoptosis pathway. Bcl-xL inhibits the activation of Bax and Bak, preserving mitochondrial outer membrane integrity. In contrast, Bcl-xS can inhibit Bcl-xL and promote the activation of Bax and Bak, resulting in the loss of mitochondrial outer membrane integrity and cell apoptosis [8].
BAX knockout leads to perturbation in mitochondrial homeostasis, energy production, apoptosis, and venetoclax resistance. Inactivation of BAX hinders the building of effective mitochondrial outer membrane permeabilization (MOMP) during apoptosis induced by venetoclax, a drug targeting BCL2 [9].
Bnip3, a protein involved in mitophagy and apoptosis signaling, has a dual functionality due to its LIR and BH3 domains. The LIR domain of Bnip3 induces mitophagy, while the BH3 domain sensitizes tBid-mediated activation of Bax, leading to ROS generation and caspase activation in the apoptotic pathway. The balance between mitophagy and apoptosis is regulated by the level of Bnip3 LIR activity [10].
These viewpoints provide an overview of BAX's role in apoptosis regulation, resistance to pro-apoptotic signals, and its involvement in mitochondrial dynamics and venetoclax response.
Figure [1]
Figure [2]
Figure [3]
Figure [4]
Figure [5]
Figure [6]
Figure [7]
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Figure [9]
Figure [10]
Note: If you are interested in the full version of this target analysis report, or if you'd like to learn how our AI-powered BDE-Chem can design therapeutic molecules to interact with the BAX target at a cost 90% lower than traditional approaches, please feel free to contact us at BD@silexon.ai.
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